CARMOFUR

Details

Stereochemistry	ACHIRAL
Molecular Formula	C11H16FN3O3
Molecular Weight	257.2614
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCCCCCNC(=O)N1C=C(F)C(=O)NC1=O

InChI

InChIKey=AOCCBINRVIKJHY-UHFFFAOYSA-N

InChI=1S/C11H16FN3O3/c1-2-3-4-5-6-13-10(17)15-7-8(12)9(16)14-11(15)18/h7H,2-6H2,1H3,(H,13,17)(H,14,16,18)

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB09010
Curator's Comment: Description was created based on several sources, including http://www.google.com/patents/US20130109707 and http://www.ncbi.nlm.nih.gov/pubmed/16155120

Carmofur, also known as 5-fluoro-N-hexyl-2,4-dioxo-pyrimidine-1-carboxamide and as 1-hexylcarbamoyl-5-fluorouracil, is a pyrimidine analogue which acts as an antineoplastic agent through inhibition of thymidylate synthase. It has been used in the treatment of breast and colorectal cancer. Carmofur is approved in Japan for the treatment of cancer.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Acid ceramidase 1 Target ID: CHEMBL2331070 Sources: http://www.ncbi.nlm.nih.gov/pubmed/23301156	Inhibitor 8504		29.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Pancreatic cancer 98 Sources: http://www.ncbi.nlm.nih.gov/pubmed/1801884	Primary	Phase II 1147	Unknown Approved Use Unknown
Gastric cancer 53 Sources: http://www.ncbi.nlm.nih.gov/pubmed/2239802	Primary	Approved 8583	Carmofur Approved Use Gastric, colorectal, breast cancer Launch Date 1981
Breast cancer 432 Sources: http://www.ncbi.nlm.nih.gov/pubmed/7887639	Primary	Approved 8583	Carmofur Approved Use Gastric, colorectal, breast cancer Launch Date 1981

AUC

Value	Dose	Co-administered	Analyte	Population
6.51 μg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/2948036	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		CARMOFUR plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.05 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/2948036	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		CARMOFUR plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
500 mg/m2 1 times / day multiple, oral Studied dose Dose: 500 mg/m2, 1 times / day Route: oral Route: multiple Dose: 500 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2239802/	unhealthy, 17-70 years Health Status: unhealthy Age Group: 17-70 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/2239802/	Other AEs: Bladder irritation, Flushing... Other AEs: Bladder irritation (13.9%) Flushing (10.4%) Dizziness (7%) Nausea (6.1%) Fatigue (4.3%) Thrombocytopenia (1.7%) Appetite lost (1.7%) Diarrhea (1.7%) Defecation urgency (1.7%) Hematuria (0.9%) Gastric pain (0.9%) Constipation (0.9%) Angina (0.9%) Antabuse effect (0.9%) Sources: https://pubmed.ncbi.nlm.nih.gov/2239802/
300 mg 1 times / day multiple, oral Studied dose Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/16823593/	unhealthy, 49-74 years Health Status: unhealthy Age Group: 49-74 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/16823593/	Other AEs: Anorexia, Nausea and vomiting... Other AEs: Anorexia (grade 3, 1%) Nausea and vomiting (grade 3, 0.7%) Diarrhea (grade 3, 1%) Skin disorder (grade 3, 0.5%) Respiratory symptom (grade 3, 0.7%) Leukocytopenia (grade 3, 2.7%) Hypochromia (grade 3, 3.2%) Neutropenia (grade 3, 2.7%) Thrombocytopenia (grade 3, 3.7%) Blood urea nitrogen increased (grade 3, 1.2%) Hematuria (grade 3, 0.2%) Sources: https://pubmed.ncbi.nlm.nih.gov/16823593/
400 mg 1 times / day multiple, oral Studied dose Dose: 400 mg, 1 times / day Route: oral Route: multiple Dose: 400 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2667512/	unhealthy, 53 years Health Status: unhealthy Age Group: 53 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/2667512/	Disc. AE: Leukoencephalopathy... AEs leading to discontinuation/dose reduction: Leukoencephalopathy Sources: https://pubmed.ncbi.nlm.nih.gov/2667512/
300 mg/m2 3 times / day multiple, oral MTD Dose: 300 mg/m2, 3 times / day Route: oral Route: multiple Dose: 300 mg/m2, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11528249/	unhealthy, Median age 60 years Health Status: unhealthy Age Group: Median age 60 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/11528249/	DLT: Anemia, Neutropenia... Dose limiting toxicities: Anemia (grade 4, 22.2%) Neutropenia (grade 4, 11.1%) Thrombocytopenia (grade 4, 11.1%) Febrile neutropenia (grade 4, 11.1%) Fatigue (grade 4, 33.3%) Anorexia (grade 4, 22.2%) Diarrhea (grade 4, 11.1%) Mucositis (grade 4, 11.1%) Sources: https://pubmed.ncbi.nlm.nih.gov/11528249/
300 mg/m2 3 times / day multiple, oral MTD Dose: 300 mg/m2, 3 times / day Route: oral Route: multiple Dose: 300 mg/m2, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11528249/	unhealthy, Median age 60 years Health Status: unhealthy Age Group: Median age 60 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/11528249/	DLT: Neutropenia, Fatigue... Dose limiting toxicities: Neutropenia (grade 4, 16.7%) Fatigue (grade 4, 33.3%) Anorexia (grade 4, 16.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/11528249/
300 mg/m2 3 times / day multiple, oral MTD Dose: 300 mg/m2, 3 times / day Route: oral Route: multiple Dose: 300 mg/m2, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11528249/	unhealthy, Median age 60 years Health Status: unhealthy Age Group: Median age 60 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/11528249/	DLT: Fatigue, Diarrhea... Dose limiting toxicities: Fatigue (grade 4, 33.3%) Diarrhea (grade 4, 33.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/11528249/
400 mg/m2 3 times / day multiple, oral MTD Dose: 400 mg/m2, 3 times / day Route: oral Route: multiple Dose: 400 mg/m2, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11528249/	unhealthy, Median age 60 years Health Status: unhealthy Age Group: Median age 60 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/11528249/	DLT: Fatigue, Leukopenia... Dose limiting toxicities: Fatigue (grade 4, 44.4%) Leukopenia (grade 4, 22.2%) Neutropenia (grade 4, 11.1%) Febrile neutropenia (grade 4, 22.2%) Anorexia (grade 4, 11.1%) Diarrhea (grade 4, 44.4%) Neurological symptoms NOS (grade 4, 11.1%) Sources: https://pubmed.ncbi.nlm.nih.gov/11528249/

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OATP1B3 961 OATP1B1 1079	AC1/2 1

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
OATP1B1 1095	inhibitor 4027 Sources: https://molpharm.aspetjournals.org/content/83/6/1257 Page: -	no
OATP1B3 970	inhibitor 4027 Sources: https://molpharm.aspetjournals.org/content/83/6/1257 Page: -	no

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
AC1/2 1	substrate 4014 Sources: https://pubs.acs.org/doi/suppl/10.1021/acs.jmedchem.8b01723/suppl_file/jm8b01723_si_001.pdf Page: -	yes

PubMed

Title	Date	PubMed
Co-polymeric hydrophilic nanospheres for drug delivery: release kinetics, and cellular uptake.	2010-10	21299047
Minute liver metastases from a rectal carcinoid: A case report and review.	2010-03-27	21160856
Suppression of growth, migration and invasion of highly-metastatic human breast cancer cells by berbamine and its molecular mechanisms of action.	2009-10-01	19796390
Anti-tumor activity of carmofur water-solubilized by lactic acid oligomer-grafted pullulan nanogels.	2009-08	19928152
Immunochemotherapy with PSK and fluoropyrimidines improves long-term prognosis for curatively resected colorectal cancer.	2008-08	18771350
Delayed leukoencephalopathy with stroke-like presentation in chemotherapy recipients.	2008-05	17682013
[Leukoencephalopathy caused by antineoplastic drugs].	2008-02	18306661
[Drug-induced leukoencephalopathy].	2007-10-28	18074566
[Drug-induced leukoencephalopathy].	2007-08-10	17802714
An individual patient data meta-analysis of adjuvant therapy with uracil-tegafur (UFT) in patients with curatively resected rectal cancer.	2007-04-23	17375049
Randomized trial of the efficacy of adjuvant chemotherapy for colon cancer with combination therapy incorporating the oral pyrimidine 1-hexylcarbamoyl-5-fluorouracil.	2006-08	16823593
Significance of histologic type of primary lesion and metastatic lymph nodes as a prognostic factor in stage III colon cancer.	2006-07	16625329
[Adjuvant chemotherapy for colorectal cancer].	2006-03	16531709
Delivery of hydrophobised 5-fluorouracil derivative to brain tissue through intravenous route using surface modified nanogels.	2006-02	16608735
S-1 (TS-1) maintained complete response for approximately 10 years in a case of metastatic breast cancer.	2006	16755122
An individual patient data meta-analysis of adjuvant therapy with carmofur in patients with curatively resected colon cancer.	2005-09	16155120
[Multicenter comparative study of the recurrence-inhibitory effect of oral fluoropyrimidine drugs in patients with colorectal cancer following curative resection].	2005-07	16044962
A multicenter randomized study comparing 5-fluorouracil continuous infusion (ci) plus 1-hexylcarbamoyl-5-fluorouracil and 5-FU ci alone in colorectal cancer.	2005-07	15944779
[Postoperative changes in serum lipid levels of breast cancer and adjuvant chemotherapy].	2004-10	15508443
1-hexylcarbamoyl-5-fluorouracil + cyclophosphamide + tamoxifen versus CMF + tamoxifen in women with lymph node-positive breast cancer after primary surgery: a randomized controlled trial.	2004-10	15375502
Randomized controlled trial of the efficacy of adjuvant immunochemotherapy and adjuvant chemotherapy for colorectal cancer, using different combinations of the intracutaneous streptococcal preparation OK-432 and the oral pyrimidines 1-hexylcarbamoyl-5-fluorouracil and uracil/tegafur.	2004-04	15108041
Postoperative adjuvant use of carmofur for early breast cancer.	2003-12	15179836
[Neo-adjuvant chemotherapy with carmofur for colorectal cancer--a multi-institutional randomized controlled study].	2002-11	12465390
Raltitrexed treatment promotes systemic inflammatory reaction in patients with colorectal carcinoma.	2002-09-09	12237767
Post-operative adjuvant chemotherapy for colorectal cancer with 5-fluorouracil (5-FU) infusion combined with 1-hexylcarbamoyl-5-fluorouracil (HCFU) oral administration after curative resection.	2002-03-26	11911312
Plasma, intestine and tumor levels of 5-fluorouracil in mice bearing L1210 ascites tumor following oral administration of 5-fluorouracil, UFT (mixed compound of tegafur and uracil), carmofur and 5'-deoxy-5-fluorouridine.	2001-11	11725974
[A case of reversible carmofur-induced leukoencephalopathy].	2001-10	11725511
Docetaxel alone or orally combined with 5-fluorouracil and its derivatives: effects on mouse mammary tumor cell line MM2 in vitro and in vivo.	2001-09	11604557
Randomized, controlled trial of lateral node dissection vs. nerve-preserving resection in patients with rectal cancer after preoperative radiotherapy.	2001-09	11584199
Apoptosis and p53 overexpression in human rectal cancer; relationship with response to hyperthermo-chemo-radiotherapy.	2001-08-15	11501834
Postoperative chemoendocrine therapy for women with node-positive stage II breast cancer with combined cyclophosphamide, tamoxifen, and 1-hexylcarbamoyl-5-fluorouracil.	2001-08	11716446
Optimal duration of oral adjuvant chemotherapy with Carmofur in the colorectal cancer patients: the Kansai Carmofur Study Group trial III.	2001-08	11445841
Adjuvant chemotherapy after resection of hepatocellular carcinoma causes deterioration of long-term prognosis in cirrhotic patients: metaanalysis of three randomized controlled trials.	2001-06-15	11413528
[Inhibition of HCFU absorption after resection for gastric cancer--application of hydroxyaluminium gel].	2001-06	11432348
5-fluorouracil-induced leukoencephalopathy in patients with breast cancer.	2001-06	11410695
An individual patient data meta-analysis of long supported adjuvant chemotherapy with oral carmofur in patients with curatively resected colorectal cancer.	2001-04-11	11295105
Diffusion-weighted MR imaging of Carmofur-induced leukoencephalopathy.	2001	11734966
A phase I study of raltitrexed (Tomudex) combined with carmofur in metastatic colorectal cancer.	2001	11528249
Carmofur-induced leukoencephalopathy: MRI.	1995-11	8748897
[Clinical effects of carmofur (Mifurol) on advanced and recurrent breast cancer in a cooperative study. Research association for re-evaluation of direct effects of Mifurol on breast cancer].	1995-03	7887639
Carmofur-induced organic mental disorders.	1990-12	2096243
A case of carmofur-induced leukoencephalopathy--MR images and CT findings.	1989-09	2487975
Leukoencephalopathy following treatment with carmofur: a case report and review of the Japanese literature.	1989-06	2667512
[A case of leukoencephalopathy caused by HCFU].	1988-05	3379758
Subacute leucoencephalopathy induced by carmofur, a 5-fluorouracil derivative.	1987-08	3309192
[Clinical evaluation of 1-hexylcarbamoyl-5-fluorouracil (HCFU) in hepatocellular carcinoma].	1984-11	6093712
Phase I study of a new antitumor drug, 1-hexylcarbamoyl-5-fluorouracil (HCFU), administered orally: an HCFU clinical study group report.	1980-08-01	7448823

Patents

Sample Use Guides

In Vivo Use Guide

Orally 300-500 mg/m2 daily for 6 weeks for advanced gastrointestinal cancer treatment

Route of Administration: Oral

In Vitro Use Guide

When exposed for 24 h to carmofur (1–100 mM), AC-overexpressing HEK 293 cells showed a markedly reduced ceramide accumulation and cell death relative to control cells subjected to the same treatment.

Name

Type

Language

MIFUROL

Preferred Name

English

CARMOFUR

Official Name

English

carmofur [INN]

Common Name

English

CARMOFUR [MI]

Common Name

English

NSC-758963

Code

English

CARMOFUR [JAN]

Common Name

English

CARMOFUR [MART.]

Common Name

English

Carmofur [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1557